NF-kB Regulation and the Chaperone System Mediate Restorative Effects of the Probiotic Lactobacillus fermentum LF31 in the Small Intestine and Cerebellum of Mice with Ethanol-Induced Damage
Letizia Paladino, Francesca Rappa, Rosario Barone, Filippo Macaluso, Francesco Paolo Zummo, Sabrina David, Marta Anna Szychlinska, Fabio Bucchieri, Everly Conway de Macario, Alberto J.L. Macario, Francesco Cappello, Antonella Marino
Abstract
Probiotics are live microorganisms that yield health benefits when consumed, generally by improving or restoring the intestinal flora (microbiota) as part of the muco-microbiotic layer of the bowel. In this work, mice were fed with ethanol alone or in combination with the probiotic Lactobacillus fermentum (L. fermentum) for 12 weeks. The modulation of the NF-κB signaling pathway with the induction of Hsp60, Hsp90, and IkB-α by the probiotic occurred in the jejunum. L. fermentum inhibited IL-6 expression and downregulated TNF-α transcription. NF-κB inactivation concurred with the restoration of the intestinal barrier, which had been damaged by ethanol, via the production of tight junction proteins, ameliorating the ethanol-induced intestinal permeability. The beneficial effect of the probiotic on the intestine was repeated for the cerebellum, in which downregulation of glial inflammation-related markers was observed in the probiotic-fed mice. The data show that L. fermentum exerted anti-inflammatory and cytoprotective effects in both the small intestine and the cerebellum, by suppressing ethanol-induced increased intestinal permeability and curbing neuroinflammation. The results also suggest that L. fermentum could be advantageous, along with the other available means, for treating intestinal diseases caused by stressors associated with inflammation and dysbiosis.